HRT linked to lower dementia risk in major study of 183,000 women

A major new study involving more than 183,000 women has found an association between hormone replacement therapy (HRT) and a lower risk of dementia, including Alzheimer’s disease: although researchers stress the findings do not prove HRT prevents the condition.

Researchers from the University of East Anglia and University of Exeter analysed health data from 183,450 postmenopausal women in the UK Biobank, following them for an average of 13.3 years.

During more than 2.4 million person-years of follow-up, 3,948 cases of dementia were identified.

Published in the journal Alzheimer’s & Dementia, the study found women who had used HRT for at least one year had about a 10 per cent lower risk of developing dementia from any cause compared with women who had never used it. The researchers also reported a 16 per cent lower risk of Alzheimer’s disease among HRT users.

Some women showed a stronger association

The results were particularly striking among women who had experienced surgical menopause, such as following removal of the ovaries.

In that group, HRT use was associated with a 26 per cent lower risk of dementia.

Women who had experienced lower natural oestrogen exposure during their lives — because, for example, they began menstruating later or experienced menopause earlier — also showed a stronger association.

Genetics appeared to play a role, too. The link between HRT and lower dementia risk was stronger among women carrying the APOE4 gene variant, one of the best-known genetic risk factors for Alzheimer’s disease.

Timing may also be important, with the researchers finding the strongest association among women who began HRT between the ages of 46 and 56.

An important note of caution

While the size and duration of the study make the findings significant, they should not be interpreted as evidence that HRT prevents dementia.

This was an observational study, meaning it can identify associations but cannot establish cause and effect. Other differences between women who use HRT and those who do not could influence dementia risk.

The wider evidence also remains mixed. A recent systematic review and meta-analysis found no evidence that menopausal hormone therapy either increased or decreased overall dementia risk in postmenopausal women.

The new findings therefore add an important piece to an evolving scientific picture rather than settling the question.

Women should not start, stop or change HRT for the purpose of preventing dementia on the basis of this study and should discuss their individual benefits and risks with their doctor.